tbuckley/cabot-search huggingface dataset:
Human Infection Challenge with Serotype 3 Pneumococcus
Authors: Ryan E. Robinson, Elena Mitsi, Elissavet Nikolaou, Sherin Pojar, Tao Chen, Jesús Reiné, Tinashe K. Nyazika, James Court, Kelly Davies, Madlen Farrar, Patricia Gonzalez-Dias, Josh Hamilton, Helen Hill, Lisa Hitchins, Ashleigh Howard, Angela Hyder-Wright, Maia Lesosky, Konstantinos Liatsikos, Agnes Matope, Daniella McLenaghan, Christopher Myerscough, Annabel Murphy, Carla Solórzano, Duolao Wang, Hassan Burhan, Manish Gautam, Elizabeth Begier, Christian Theilacker, Rohini Beavon, Annaliesa S. Anderson, Bradford D. Gessner, Stephen B. Gordon, Andrea M. Collins, Daniela M. Ferreira
Journal: American Journal of Respiratory and Critical Care Medicine (2022)

Rationale:Streptococcus pneumoniae serotype 3 (SPN3) is a cause of invasive pneumococcal disease and associated with low carriage rates. Following the introduction of pediatric 13-valent pneumococcal conjugate vaccine (PCV13) programs, SPN3 declines are less than other vaccine serotypes and incidence has increased in some populations coincident with a shift in predominant circulating SPN3 clade, from I to II. A human challenge model provides an effective means for assessing the impact of PCV13 on SPN3 in the upper airway. Objectives: To establish SPN3's ability to colonize the nasopharynx using different inoculum clades and doses, and the safety of an SPN3 challenge model. Methods: In a human challenge study involving three well-characterized and antibiotic-sensitive SPN3 isolates (PFESP306 [clade Ia], PFESP231 [no clade], and PFESP505 [clade II]), inoculum doses (10,000, 20,000, 80,000, and 160,000 cfu/100 μl) were escalated until maximal colonization rates were achieved, with concurrent acceptable safety. Measurement and Main Results: Presence and density of experimental SPN3 nasopharyngeal colonization in nasal wash samples, assessed using microbiological culture and molecular methods, on Days 2, 7, and 14 postinoculation. A total of 96 healthy participants (median age 21, interquartile range 19-25) were inoculated (n = 6-10 per dose group, 10 groups). Colonization rates ranged from 30.0-70.0% varying with dose and isolate. 30.0% (29/96) reported mild symptoms (82.8% [24/29] developed a sore throat); one developed otitis media requiring antibiotics. No serious adverse events occurred. Conclusions: An SPN3 human challenge model is feasible and safe with comparable carriage rates to an established Serotype 6B human challenge model. SPN3 carriage may cause mild upper respiratory symptoms.
The return of the helix: an evaluation of motorized spiral enteroscopy in actual daily clinical practice; a few points to “torque” about and ponder upon…
Authors: Edward J. Despott, Alberto Murino
Journal: Endoscopy (2022)

Although Akerman et al. first reported on the concept of motorized spiral enteroscopy (MSE) over a decade ago [1], it has only recently been introduced into actual clinical practice [2] and our understanding of its safety and performance is still being fine-tuned. In this issue of Endoscopy, Al-Toma et al., from the Netherlands, report on their multicenter prospective uncontrolled study in a "real-world" setting, with a focus on performance and safety in "all-comers," including patients with a previous history of surgery and altered anatomy [3]. Their study included 170 patients, with a median age of 64 years. The primary end points were the diagnostic and therapeutic yields (in patients with suspected small-bowel pathology on pre-enteroscopy imaging) and overall safety, as measured by adverse events. The diagnostic and therapeutic yields were 64.1 % and 53.5 %, respectively. Median procedure durations were 45 and 40 minutes for antegrade and retrograde MSE procedures, respectively. Panenteroscopy was achieved in 70.3 % of patients in whom it was attempted, warranting a bidirectional approach in 42.1 %. Of the whole cohort, 34 patients had post-surgical altered small-bowel anatomy (20 %). Altered anatomy was present in 11 of the 45 patients (24.4 %) in whom panenteroscopy was achieved. There were no differences in any of the outcomes in the nonsurgical and surgical subgroups. The authors reported that no major adverse events (defined as perforation, bleeding warranting transfusion, pancreatitis, and unplanned hospital admission) occurred within 30 days of follow-up. Minor adverse events (defined as mucosal abrasion, superficial lacerations, self-limiting pharyngitis, abdominal discomfort, nausea, and vomiting) occurred in 15.8 %.
Theory of the Multiregional Neocortex: Large-Scale Neural Dynamics and Distributed Cognition
Authors: Xiao-Jing Wang
Journal: Annual Review of Neuroscience (2022)

The neocortex is a complex neurobiological system with many interacting regions. How these regions work together to subserve flexible behavior and cognition has become increasingly amenable to rigorous research. Here, I review recent experimental and theoretical work on the modus operandi of a multiregional cortex. These studies revealed several general principles for the neocortical interareal connectivity, low-dimensional macroscopic gradients of biological properties across cortical areas, and a hierarchy of timescales for information processing. Theoretical work suggests testable predictions regarding differential excitation and inhibition along feedforward and feedback pathways in the cortical hierarchy. Furthermore, modeling of distributed working memory and simple decision-making has given rise to a novel mathematical concept, dubbed bifurcation in space, that potentially explains how different cortical areas, with a canonical circuit organization but gradients of biological heterogeneities, are able to subserve their respective (e.g., sensory coding versus executive control) functions in a modularly organized brain.
A therapeutic DC vaccine with maintained immunological activity exhibits robust anti-tumor efficacy
Authors: Yichao Lu, Yingying Shi, Yu Liu, Zhenyu Luo, Junlei Zhang, Mengshi Jiang, Xiang Li, Xu Liu, Xuemeng Guo, Bing Qin, Hang Yin, Yongzhong Du, Yunqing Qiu, Yan Lou, Guannan Guan, Lihua Luo, Jian You
Journal: Journal of Controlled Release (2022)
The interplay of post-acute COVID-19 syndrome and aging: a biological, clinical and public health approach
Authors: Giovanni Guaraldi, Jovana Milic, Matteo Cesari, Leonard Leibovici, Federica Mandreoli, Paolo Missier, Renzo Rozzini, Anna Maria Cattelan, Federico Motta, Cristina Mussini, Andrea Cossarizza
Journal: Ageing Research Reviews (2022)
Evolution of Human-Specific Alleles Protecting Cognitive Function of Grandmothers
Authors: Sudeshna Saha, Naazneen Khan, Troy Comi, Andrea Verhagen, Aniruddha Sasmal, Sandra Diaz, Hai Yu, Xi Chen, Joshua M Akey, Martin Frank, Pascal Gagneux, Ajit Varki
Journal: Molecular Biology and Evolution (2022)

Abstract The myelomonocytic receptor CD33 (Siglec-3) inhibits innate immune reactivity by extracellular V-set domain recognition of sialic acid (Sia)-containing “self-associated molecular patterns” (SAMPs). We earlier showed that V-set domain-deficient CD33-variant allele, protective against late-onset Alzheimer’s Disease (LOAD), is derived and specific to the hominin lineage. We now report multiple hominin-specific CD33 V-set domain mutations. Due to hominin-specific, fixed loss-of-function mutation in the CMAH gene, humans lack N-glycolylneuraminic acid (Neu5Gc), the preferred Sia-ligand of ancestral CD33. Mutational analysis and molecular dynamics (MD)-simulations indicate that fixed change in amino acid 21 of hominin V-set domain and conformational changes related to His45 corrected for Neu5Gc-loss by switching to N-acetylneuraminic acid (Neu5Ac)-recognition. We show that human-specific pathogens Neisseria gonorrhoeae and Group B Streptococcus selectively bind human CD33 (huCD33) as part of immune-evasive molecular mimicry of host SAMPs and that this binding is significantly impacted by amino acid 21 modification. In addition to LOAD-protective CD33 alleles, humans harbor derived, population-universal, cognition-protective variants at several other loci. Interestingly, 11 of 13 SNPs in these human genes (including CD33) are not shared by genomes of archaic hominins: Neanderthals and Denisovans. We present a plausible evolutionary scenario to compile, correlate, and comprehend existing knowledge about huCD33-evolution and suggest that grandmothering emerged in humans.
Randomized Phase II Trial of Proton Craniospinal Irradiation Versus Photon Involved-Field Radiotherapy for Patients With Solid Tumor Leptomeningeal Metastasis
Authors: Jonathan T. Yang, N. Ari Wijetunga, Elena Pentsova, Suzanne Wolden, Robert J. Young, Denise Correa, Zhigang Zhang, Junting Zheng, Alexa Steckler, Weronika Bucwinska, Ashley Bernstein, Allison Betof Warner, Helena Yu, Mark G. Kris, Andrew D. Seidman, Jessica A. Wilcox, Rachna Malani, Andrew Lin, Lisa M. DeAngelis, Nancy Y. Lee, Simon N. Powell, Adrienne Boire
Journal: Journal of Clinical Oncology (2022)

Photon involved-field radiotherapy (IFRT) is the standard-of-care radiotherapy for patients with leptomeningeal metastasis (LM) from solid tumors. We tested whether proton craniospinal irradiation (pCSI) encompassing the entire CNS would result in superior CNS progression-free survival (PFS) compared with IFRT.
Signaling Pathways in Neurovascular Development
Authors: Amir Rattner, Yanshu Wang, Jeremy Nathans
Journal: Annual Review of Neuroscience (2022)

During development, the central nervous system (CNS) vasculature grows to precisely meet the metabolic demands of neurons and glia. In addition, the vast majority of the CNS vasculature acquires a unique set of molecular and cellular properties—collectively referred to as the blood–brain barrier—that minimize passive diffusion of molecules between the blood and the CNS parenchyma. Both of these processes are controlled by signals emanating from neurons and glia. In this review, we describe the nature and mechanisms-of-action of these signals, with an emphasis on vascular endothelial growth factor (VEGF) and beta-catenin (canonical Wnt) signaling, the two best-understood systems that regulate CNS vascular development. We highlight foundational discoveries, interactions between different signaling systems, the integration of genetic and cell biological studies, advances that are of clinical relevance, and questions for future research.
DNA Methylation Profiling Identifies Subgroups of Lung Adenocarcinoma with Distinct Immune Cell Composition, DNA Methylation Age, and Clinical Outcome
Authors: Kayla Guidry, Varshini Vasudevaraja, Kristen Labbe, Hussein Mohamed, Jonathan Serrano, Brett W. Guidry, Michael DeLorenzo, Hua Zhang, Jiehui Deng, Soumyadip Sahu, Christina Almonte, Andre L. Moreira, Aristotelis Tsirigos, Thales Papagiannakopoulos, Harvey Pass, Matija Snuderl, Kwok-Kin Wong
Journal: Clinical Cancer Research (2022)

Abstract Purpose: Lung adenocarcinoma (LUAD) is a clinically heterogeneous disease, which is highlighted by the unpredictable recurrence in low-stage tumors and highly variable responses observed in patients treated with immunotherapies, which cannot be explained by mutational profiles. DNA methylation–based classification and understanding of microenviromental heterogeneity may allow stratification into clinically relevant molecular subtypes of LUADs. Experimental Design: We characterize the genome-wide DNA methylation landscape of 88 resected LUAD tumors. Exome sequencing focusing on a panel of cancer-related genes was used to genotype these adenocarcinoma samples. Bioinformatic and statistical tools, the immune cell composition, DNA methylation age (DNAm age), and DNA methylation clustering were used to identify clinically relevant subgroups. Results: Deconvolution of DNA methylation data identified immunologically hot and cold subsets of LUADs. In addition, concurrent factors were analyzed that could affect the immune microenvironment, such as smoking history, ethnicity, or presence of KRAS or TP53 mutations. When the DNAm age was calculated, a lower DNAm age was correlated with the presence of a set of oncogenic drivers, poor overall survival, and specific immune cell populations. Unsupervised DNA methylation clustering identified six molecular subgroups of LUAD tumors with distinct clinical and microenvironmental characteristics. Conclusions: Our results demonstrate that DNA methylation signatures can stratify LUAD into clinically relevant subtypes, and thus such classification of LUAD at the time of resection may lead to better methods in predicting tumor recurrence and therapy responses.
Functional Ultrasound Neuroimaging
Authors: Gabriel Montaldo, Alan Urban, Emilie Macé
Journal: Annual Review of Neuroscience (2022)

Functional ultrasound (fUS) is a neuroimaging method that uses ultrasound to track changes in cerebral blood volume as an indirect readout of neuronal activity at high spatiotemporal resolution. fUS is capable of imaging head-fixed or freely behaving rodents and of producing volumetric images of the entire mouse brain. It has been applied to many species, including primates and humans. Now that fUS is reaching maturity, it is being adopted by the neuroscience community. However, the nature of the fUS signal and the different implementations of fUS are not necessarily accessible to nonspecialists. This review aims to introduce these ultrasound concepts to all neuroscientists. We explain the physical basis of the fUS signal and the principles of the method, present the state of the art of its hardware implementation, and give concrete examples of current applications in neuroscience. Finally, we suggest areas for improvement during the next few years.
Immune determinants of chronic sequelae after respiratory viral infection
Authors: Harish Narasimhan, Yue Wu, Nick P. Goplen, Jie Sun
Journal: Science Immunology (2022)

The acute effects of various respiratory viral infections have been well studied, with extensive characterization of the clinical presentation as well as viral pathogenesis and host responses. However, over the course of the recent COVID-19 pandemic, the incidence and prevalence of chronic sequelae after acute viral infections have become increasingly appreciated as a serious health concern. Post-acute sequelae of COVID-19, alternatively described as "long COVID-19," are characterized by symptoms that persist for longer than 28 days after recovery from acute illness. Although there exists substantial heterogeneity in the nature of the observed sequelae, this phenomenon has also been observed in the context of other respiratory viral infections including influenza virus, respiratory syncytial virus, rhinovirus, severe acute respiratory syndrome coronavirus, and Middle Eastern respiratory syndrome coronavirus. In this Review, we discuss the various sequelae observed following important human respiratory viral pathogens and our current understanding of the immunological mechanisms underlying the failure of restoration of homeostasis in the lung.
Corrigendum to “Repairing critical-sized calvarial defects with BMSCs modified by a constitutively active form of hypoxia-inducible factor-1a and a phosphate cement scaffold” [Biomaterials, 32(36) (2011) 9707–9718]
Authors: Duohong Zou, Zhiyuan Zhang, Jiacai He, Siheng Zhu, Shaoyi Wang, Wenjie Zhang, Jian Zhou, Yuanjin Xu, Yan Huang, Yuanyin Wang, Wei Han, Yong Zhou, Shuhong Wang, Sulan You, Xinquan Jiang, Yuanliang Huang
Journal: Biomaterials (2022)
Comparison of pharmacologic therapies alone versus operative techniques in combination with pharmacologic therapies for postoperative analgesia in patients undergoing laparoscopic cholecystectomy: A randomized controlled trial
Authors: Hyun-Chang Kim, Young Song, Jong Seok Lee, Myeong Eun Jeong, Yongmin Lee, Jin Hong Lim, Do-Hyeong Kim
Journal: International Journal of Surgery (2022)

Laparoscopic cholecystectomy (LC) causes moderate pain. Various operative analgesic techniques and pharmacologic treatments can reduce postoperative pain. This single-center, single-surgeon randomized controlled study aimed to assess the efficacy of combined operative analgesic techniques and pharmacologic analgesia in decreasing pain in patients undergoing LC. Fifty-nine patients scheduled for LC were assigned into two groups. In the pharmacologic analgesia (P) group (n = 29), patients were treated with pharmacologic intervention, including preoperative celecoxib (200 mg), intraoperative acetaminophen (1 g), and dexamethasone (8 mg). In the operative analgesic treatments with pharmacologic analgesia (OP) group (n = 30), patients were treated with both operative analgesic techniques and pharmacologic analgesia, including low-pressure pneumoperitoneum, intraperitoneal normal saline irrigation, and aspiration of intraperitoneal carbon dioxide. The area under the curve (AUC) of pain score for postoperative 24 h was assessed at 0, 2, 6, and 24 h post-operation. The analgesic requirements and sleep quality at postoperative day 1 were assessed. The AUC/24 h of pain scores at rest and on cough were lower in the OP group (p < 0.001 and p = 0.001, respectively). The pain scores at rest were lower in the OP group at postoperative 2, 6, and 24 h (p = 0.001, p = 0.001, and p = 0.048, respectively). The pain scores on cough were lower in the OP group at postoperative 2 and 6 h (p = 0.004 and p = 0.008, respectively). Analgesic requirements were comparable. The sleep quality score at postoperative day 1 was higher in the OP group (56 ± 18 vs. 67 ± 15, absolute difference, 10; 95% confidence interval, 2 to 19; p = 0.017). Combined operative analgesic therapies and pharmacologic analgesia compared to pharmacologic analgesia alone decreased pain scores and increased sleep quality in patients undergoing LC.
Vitamin C supramolecular hydrogel for enhanced cancer immunotherapy
Authors: Han Zhang, Kai Liu, Yimou Gong, Wenjun Zhu, Jiafei Zhu, Feng Pan, Yu Chao, Zhishen Xiao, Yanbin Liu, Xianwen Wang, Zhuang Liu, Yang Yang, Qian Chen
Journal: Biomaterials (2022)
Exotic viral hepatitis: A review on epidemiology, pathogenesis, and treatment
Authors: Leanne P.M. van Leeuwen, Wesley de Jong, Laura Doornekamp, Eric C.M. van Gorp, Pieter J. Wismans, Marco Goeijenbier
Journal: Journal of Hepatology (2022)

Certain "exotic" viruses are known to cause clinical diseases with potential liver involvement. These include viruses, beyond regular hepatotropic viruses (hepatitis A, -B(D), -C, -E, cytomegalovirus, Epstein-Barr virus), that can be found in (sub)tropical areas and can cause "exotic viral hepatitis". Transmission routes typically involve arthropods (Crimean Congo haemorrhagic fever, dengue, Rift Valley fever, yellow fever). However, some of these viruses are transmitted by the aerosolised excreta of rodents (Hantavirus, Lassa fever), or via direct contact or contact with bodily fluids (Ebola). Although some exotic viruses are associated with high fatality rates, such as Ebola for example, the clinical presentation of most exotic viruses can range from mild flu-like symptoms, in most cases, right through to being potentially fatal. A smaller percentage of people develop severe disease with haemorrhagic fever, possibly with (fulminant) hepatitis. Liver involvement is often caused by direct tropism for hepatocytes and Kupffer cells, resulting in virus-mediated and/or immune-mediated necrosis. In all exotic hepatitis viruses, PCR is the most sensitive diagnostic method. The determination of IgM/IgG antibodies is a reasonable alternative, but cross-reactivity can be a problem in the case of flaviviruses. Licenced vaccines are available for yellow fever and Ebola, and they are currently under development for dengue. Therapy for exotic viral hepatitis is predominantly supportive. To ensure that preventive measures can be introduced to control possible outbreaks, the timely detection of these viruses is very important.
Safety and efficacy of mosunetuzumab, a bispecific antibody, in patients with relapsed or refractory follicular lymphoma: a single-arm, multicentre, phase 2 study
Authors: Lihua E Budde, Laurie H Sehn, Matthew Matasar, Stephen J Schuster, Sarit Assouline, Pratyush Giri, John Kuruvilla, Miguel Canales, Sascha Dietrich, Keith Fay, Matthew Ku, Loretta Nastoupil, Chan Yoon Cheah, Michael C Wei, Shen Yin, Chi-Chung Li, Huang Huang, Antonia Kwan, Elicia Penuel, Nancy L Bartlett
Journal: The Lancet Oncology (2022)
Sociodemographic and geographic differences in the US epidemiology of autoimmune hepatitis with and without cirrhosis
Authors: Therese Bittermann, James D. Lewis, Cynthia Levy, David S. Goldberg
Journal: Hepatology (2022)

Background and Aims: Data on the epidemiology of autoimmune hepatitis (AIH) in the United States are limited. This study investigated the sociodemographic and geographic factors associated with AIH incidence and prevalence with and without cirrhosis. Approach and Results: In a retrospective cohort of adults in the Optum Clinformatics Data Mart (2009–2018), we identified AIH cases using a validated claims‐based algorithm. Incidence and prevalence were compared between sociodemographic subgroups. Logistic regression evaluated the association of US Census Division with AIH incidence and the factors associated with incident AIH with cirrhosis. From 2009 to 2018, the age‐ and sex‐standardized prevalence of AIH in the Optum cohort was 26.6 per 100,000 persons with an incidence of 4.0 per 100,000 person‐years. AIH incidence increased earlier among Hispanics (age 50–59 years) and later among Asians (≥80 years). Adjusted AIH incidence was higher in the Mountain Division (odds ratio [OR] 1.17) and lower in the Pacific (OR 0.68), Middle Atlantic (OR 0.81), and West North Central Divisions (OR 0.86 vs. East North Central; p &lt; 0.001). Male sex (OR 1.31, p = 0.003), Black race (OR 1.32, p = 0.022), and Hispanic ethnicity (OR 1.37 vs. non‐Hispanic White, p = 0.009) were associated with incident AIH with cirrhosis. Incident AIH with cirrhosis was greater in the West South Central Division (OR 1.30 vs. South Atlantic; p = 0.008). Conclusions: AIH epidemiology differs according to sociodemographic and geographic factors in the United States. Studies are needed to determine the genetic, epigenetic, and environmental factors underlying the heterogeneity in AIH risk and outcomes.
Outbreak of sexually transmitted, extensively drug-resistant Shigella sonnei in the UK, 2021–22: a descriptive epidemiological study
Authors: Hannah Charles, Mateo Prochazka, Katie Thorley, Adam Crewdson, David R Greig, Claire Jenkins, Anais Painset, Helen Fifer, Lynda Browning, Paul Cabrey, Robert Smith, Daniel Richardson, Laura Waters, Katy Sinka, Gauri Godbole, Helen Corkin, Asha Abrahams, Holly LeBlond, Janice Lo, Amelia Holgate, John Saunders, Gunveer Plahe, Amoolya Vusirikala, Freddy Green, Mike King, Rediat Tewolde, Andrew Jajja
Journal: The Lancet Infectious Diseases (2022)
TRAIL &amp; EGFR affibody dual-display on a protein nanoparticle synergistically suppresses tumor growth
Authors: Heejin Jun, Eunjung Jang, Hansol Kim, Mirae Yeo, Seong Guk Park, Jaehyeok Lee, Kyeong Jin Shin, Young Chan Chae, Sebyung Kang, Eunhee Kim
Journal: Journal of Controlled Release (2022)
Comparison of four assays for human papillomavirus detection in the anal canal
Authors: I. Mary Poynten, Fengyi Jin, Monica Molano, Dorothy A. Machalek, Jennifer M. Roberts, Richard J. Hillman, Alyssa Cornall, Samuel Phillips, David J. Templeton, Carmella Law, Christopher K. Fairley, Andrew E. Grulich, Suzanne M. Garland
Journal: Clinical Microbiology and Infection (2022)
Deucravacitinib versus placebo and apremilast in moderate to severe plaque psoriasis: Efficacy and safety results from the 52-week, randomized, double-blinded, placebo-controlled phase 3 POETYK PSO-1 trial
Authors: April W. Armstrong, Melinda Gooderham, Richard B. Warren, Kim A. Papp, Bruce Strober, Diamant Thaçi, Akimichi Morita, Jacek C. Szepietowski, Shinichi Imafuku, Elizabeth Colston, John Throup, Sudeep Kundu, Steve Schoenfeld, Misti Linaberry, Subhashis Banerjee, Andrew Blauvelt
Journal: Journal of the American Academy of Dermatology (2022)